# The Role of Reproductive Aging for Racial Differences in AD/ADRD from Midlife to Older Age

> **NIH NIH K99** · STANFORD UNIVERSITY · 2024 · $131,004

## Abstract

PROJECT SUMMARY
The prevalence of Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD) is predicted
to nearly triple to 152.8 million cases worldwide by 2050. Women have double the risk versus men, and as
early as midlife, Black individuals have nearly double the risk versus White individuals. For women, the midlife
(~40-60 yrs.) is characterized by the menopausal transition, accompanied by the loss of potentially neuro-
protective and cardio-protective sex hormones. Earlier menopause means earlier exposure to decreased sex
hormones and may increase AD/ADRD risk. Further, reproductive surgeries (hysterectomy and/or bilateral
oophorectomy) can prematurely induce menopause, resulting in the sudden and often complete loss of
hormones, and may be a modifiable risk factor for AD/ADRD. Data suggest that Black women have earlier
menopause than White women – approximately 1 year for natural and up to 10 years earlier for surgical
menopause. Historical and existing racial bias may contribute to higher prevalence and timing of surgical
menopause in Black women. The few studies of menopause and long-term AD/ADRD risk are limited due to
potential bias in the measurement of menopausal age/type, bias due to selection into later life studies,
particularly affecting Black women, and little data to assess relations to disparities. The proposed project will
comprehensively assess the contribution of early menopause to overall risk and Black-White disparities in
AD/ADRD diagnoses (K99) and development (R00) by harmonizing data from 25,051 women (30% Black) in 3
cohorts: Study of Women’s Health Across the Nation (SWAN, menopausal transition to 75+ yrs.), Women’s
Health Initiative (post-menopause to 80+ yrs.) and Cardiovascular Health Study (65+ yrs.). Harmonizing
cohorts with adequate sample size to gauge disparities and “gold-standard” measurements of menopause
(SWAN) and AD/ADRD (adjudicated diagnoses, neurocognitive tests over time, and neuroimaging markers of
AD/ADRD) while applying methods that I previously developed to account for selection bias, will address prior
limitations. This proposal will ensure I get the training I need as a lifecourse social epidemiologist to work
independently with AD/ADRD data, to further address bias limitations in lifecourse data, and to estimate causal
impacts on disparities. Through the K99/R00 award, I will leverage the expertise of my mentors and my prior
training in single cohort longitudinal methods and lifecourse disparities to gain additional training in 1)
AD/ADRD diagnoses and development, 2) multi-cohort harmonization/pooling, and 3) causal intervention
modeling. Completion of this proposal will result in scientific presentations, publications, and preliminary data
to successfully compete for R01 funding that examines cardio-metabolic mediators of reproductive aging and
AD/ADRD disparities. Results will elucidate unique midlife targets for prevention in women; supporting a
potential paradigm shift fo...

## Key facts

- **NIH application ID:** 10983684
- **Project number:** 1K99AG084897-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Alexis Reeves
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $131,004
- **Award type:** 1
- **Project period:** 2024-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10983684

## Citation

> US National Institutes of Health, RePORTER application 10983684, The Role of Reproductive Aging for Racial Differences in AD/ADRD from Midlife to Older Age (1K99AG084897-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10983684. Licensed CC0.

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